All ETDs from UAB

Advisory Committee Chair

Louise Chow

Advisory Committee Members

Thomas Broker

David Crawford

Igor Chesnokov

Fang-Tsyr Lin

Weei-Chin Lin

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Papillomaviruses (PV) are prevalent pathogens that infect human or animal squamous epithelia. Its genome is a double strand circular DNA of approximately 7.9 kb. It contains origin of replication (ori) and encodes early viral proteins for viral DNA amplication, and late capsid proteins for packaging viron. The viral DNA replicates as extrachromosomal nuclear plasmid in the host cell. Infections by low risk virus, such as HPV-6 and -11, can result in benign papillomas, condylomata, and low grade squamous intraepithelial dysplasias (SIL), whereas infection by high risk virus, such as HPV-16 and -18, can progress to high grade SIL, carcinoma in situ, and cancers in which the viral genome may integrate into the host chromosome. Over 99% of cervical cancers are associated with high risk HPV infection. Currently, there is no reliable therapeutic treatment to HPV infections. Thus, it is important to have a thorough understanding on the regulation of viral DNA replication. HPV DNA replication required host DNA replication machinery and two of the viral proteins, the E2 ori binding protein and E1 replicative DNA helicase. E1 is a 68 kDa nuclear phosphoprotein and due to its high molecular weight, it can not enter nucleus by passive diffusion. In this dissertation, we investigated the mechanisms and regulation of E1 nuclear import, and the potential clinical application of our finding is discussed.



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